Skip to main content

Encyclopedia of Drug Metabolism and Interactions, Volume 4, Pharmacology and Toxicology

Encyclopedia of Drug Metabolism and Interactions, Volume 4, Pharmacology and Toxicology

Alexander V. Lyubimov (Editor-in-Chief)

ISBN: 978-1-118-14977-5

Nov 2012

600 pages

Select type: Hardcover


Product not available for purchase


The ideal place to begin researching any question involving drug metabolism and interactions

The Encyclopedia of Drug Metabolism and Interactions provides essential support during all phases of drug development, from drug design to drug action and interaction within the human body. This six-volume work covers both preclinical and clinical aspects of drug metabolism and interactions. It also provides a wealth of toxicological, regulatory, and marketing information, all written and edited by leading international experts in the field.

By collecting and reviewing the current literature in the field in one expertly organized work, this encyclopedia is the ideal place to begin researching any question involving drug metabolism and interactions. Readers will find such important topics and working tools as:

  • Inhibited or induced enzymes and their impact on drug toxicity and altered response in both animal and human models
  • Effects of both genetic and non-genetic factors on drug metabolism
  • Relationships between a drug metabolism, its activation or inactivation, and a drug's potential toxicity/safety
  • Examples demonstrating all aspects of drug metabolism and interactions in silico, in vitro, in laboratory animals, and in humans
  • Methods and protocols enabling readers to perform seamless studies of metabolism and drug interactions

All articles are based on recent findings and standards of practice. By reviewing and contextualizing the current literature, the authors offer new perspectives on our current state of knowledge as well as future directions for research in drug metabolism and interactions. References at the end of each article serve as a gateway to the literature.

The Encyclopedia of Drug Metabolism and Interactions is recommended for researchers, physicians, and students at all levels. It introduces the basics to novices and explores the latest science and applications for more experienced investigators.

Contributors ix

Preface to the Encyclopedia xxiii

Preface—Volume 4 xxvii

PART VII Role of Metabolism in Toxicology and Pharmacology 1

1 Introduction: An Overview of the Role of Metabolism in Drug Toxicity 3
Sidney D. Nelson

2 Bioactivation I: Bioactivation by Cytochrome P450s 9
Deepak K. Dalvie

3 Bioactivation II: Phase I (Non-P450) 63
Matthew J. Hutzler and Matthew A. Cerny

4 Bioactivation by Phase-II-Enzyme-Catalyzed Conjugation of Xenobiotics 103
Mark P. Grillo

5 Covalent Drug–Protein Adducts: An Exploration of Their Role in Drug-Induced Liver and General Organ Toxicity 159
David C. Evans

6 Safety Testing of Drug Metabolites: A Practical Approach for the Implementation of the MIST Guidance in PKDM 205
Raju Subramanian and J. Greg Slatter

7 In Vitro Toxicity Screening in Early Drug Discovery: Importance of Metabolism and Reactive Metabolites 223
James M. McKim Jr.

8 The Application of Preclinical Toxicogenomics for Predicting and Understanding Drug-Induced Toxicity and Metabolism 251
Mark Fielden and Christine Karbowski

9 Metabonomics in Understanding Drug Metabolism and Toxicology 281
Bo Wen

10 Proteomics in Drug Discovery and Development 311
Mu Wang and Frank A. Witzmann

11 Stereochemical Elements Associated with Drug Metabolism and Toxicity 345
Larry C. Wienkers and Guy E. Padbury

PART VIII Influence of Physiological Conditions, Diseases, Drug–Food Interactions, Age, Sex, and Other Factors on Drug Metabolism and Effect 375

12 Genetics of Drug Disposition 377
Anahita Bhathena and David A. Katz

13 Drug–Drug Interactions 1: Inhibition 405
Murali Subramanian and Timothy S. Tracy

14 Clinical Implications of CYP Induction-Mediated Drug–Drug Interactions 429
Jiunn H. Lin and Jianjun Guo

15 Age-Dependent Expression of Human Drug-Metabolizing Enzymes 451
Ronald N. Hines

16 Phytochemical Modulators of Human Drug Metabolism: Drug Interactions with Fruits, Vegetables, and Botanical Dietary Supplements 485
Bill Gurley, Kim E. Fifer, and Z¨oe Gardner

17 Idiosyncratic Drug Reactions 565
Zbigniew W. Wojcinski and Jack P. Uetrecht

18 Animal Models of Idiosyncratic, Drug-Induced Liver Injury: Emphasis on the Inflammatory Stress Hypothesis 595
Wei Zou, Robert A. Roth, and Patricia E. Ganey

19 Regulation of Drug Metabolizing Enzymes and Transporters in Infection, Inflammation, and Cancer 621
Edward T. Morgan, Choon-Myung Lee, and Beatrice A. Nyagode

Index 667